4-Cyclohexyl-1,3,2-oxazaborolidine chiral accessories

Abstract

Prochiral ketones are enantioselectively reduced to chiral secondary alcohols with a compound having the formula I: where, the two R 2 groups are identical and are each a substituted or unsubstituted, aryl, alkyl, cycloalkyl or aralkyl group; and R 3 is a hydrogen atom or a substituted or unsubstituted, alkyl, aryl, aralkyl or alkoxy group; wherein the substituents on the R 2 and R 3 groups are substantially non-reactive.

What is claimed is:  
     
       1. A compound having the formula I:                    
       where, 
       the two R 2  groups are identical and are each a substituted or unsubstituted, aryl, alkyl, cycloalkyl or aralkyl group; and  
       R 3  is a hydrogen atom or a substituted or unsubstituted, alkyl, aryl, aralkyl or alkoxy group;  
       wherein the substituents on the R 2  and R 3  groups are substantially non-reactive.  
     
     
       2. The compound according to  claim 1 , where each R 2  is a phenyl, 4-methoxyphenyl, 1-naphthyl, 2-naphthyl, 1-naphthylmethyl or 2-naphthylmethyl group. 
     
     
       3. The compound according to  claim 2 , where R 3  is the hydrogen atom or a methyl, butyl, phenyl or methoxy group. 
     
     
       4. The compound according to  claim 3 , where each R 2  is the phenyl group. 
     
     
       5. The compound according to  claim 4 , where R 3  is the hydrogen atom or the methyl group. 
     
     
       6. The compound according to  claim 4 , where R 3  is the methoxy group. 
     
     
       7. The compound according to  claim 1 , wherein the alkoxy group is unsubstituted and has the formula OR 5 , where R 5  is an unsubstituted alkyl group. 
     
     
       8. A compound having the formula II:                    
       where, 
       the two R 2  groups are identical and are each a substituted or unsubstituted, aryl, alkyl, cycloalkyl or aralkyl group,  
       wherein the substituents on the two R 2  groups are substantially non-reactive.  
     
     
       9. The compound according to  claim 8 , where each R 2  is a phenyl, 4-methoxyphenyl, 1-naphthyl, 2-naphthyl, 1-naphthylmethyl or 2-naphthylmethyl group. 
     
     
       10. The compound according to  claim 9 , where each R 2  is the phenyl group. 
     
     
       11. A process for producing a compound having the formula I:                    
       where, 
       the two R 2  groups are identical and are each a substituted or unsubstituted, aryl, alkyl, cycloalkyl or aralkyl group; and  
       R 3  is a hydrogen atom or a substituted or unsubstituted, alkyl, aryl, aralkyl or alkoxy group;  
       wherein the substituents on the R 2  and R 3  groups are substantially non-reactive, the process comprising:  
       (a) reacting a (R) or (S) cyclohexylglycine ester hydrochloride or hydrobromide compound having the formula III:                    
       where, 
       R 4  is an alkyl group, and  
       Y is a chlorine or bromine atom,  
       with an organometallic reagent having the formula R 2 MgX or R 2 Li,  
       where, 
       R 2  is the same as defined for the compound having the formula I, and  
       X is a chlorine, bromine or iodine atom,  
       to form a compound having the formula II:                    
       where, 
       R 2  is the same as defined for the compound having the formula I, and  
       (b) reacting the compound having the formula II formed in step (a) with (i) BH 3 , (ii) R 3 B(OH) 2  or (BOR 3 ) 3  or (iii) B(OR 5 ) 3 , where R 3  is the same as defined for the compound having the formula I and R 5  is a substituted or unsubstituted alkyl group,  
       to form the compound having the formula I. 
     
     
       12. The process according to  claim 11 , where R 3  is an unsubstituted alkoxy group having the formula OR 5 , where R 5  is an unsubstituted alkyl group. 
     
     
       13. A process for asymmetrically reducing a prochiral ketone having the formula IV:                    
       where, 
       R L  and R S  are different and are each an unsubstituted or substituted, aryl, alkyl, aralkyl or heteroaryl group,  
       the process comprising reacting the prochiral ketone having the formula IV with borane derived from a borane reagent in the presence of a chiral accessory having the formula I:                    
        where,  
       the two R 2  groups are identical and are each a substituted or unsubstituted, aryl, alkyl, cycloalkyl or aralkyl; and  
       R 3  is a hydrogen atom or a substituted or unsubstituted, alkyl, aryl, aralkyl or alkoxy group,  
       wherein the substituents on the R 2  and R 3  groups are substantially non-reactive,  
       to form a chiral secondary alcohol having the formula V:                    
       where, 
       R L  and R S  are the same as defined above for the prochiral ketone having the formula IV.  
     
     
       14. The process according to  claim 13 , wherein R 3  is an unsubstituted alkoxy group having the formula OR 5 , where R 5  is an unsubstituted alkyl group. 
     
     
       15. The process according to  claim 13 , where the two R 2  groups are each a substituted or unsubstituted phenyl group and R 3  is a hydrogen atom or a substituted or unsubstituted, methyl or methoxy group. 
     
     
       16. The process according to  claim 13 , where R L  is the unsubstituted or substituted, aryl or heteroaryl group and R S  is the unsubstituted or substituted alkyl group. 
     
     
       17. The process according to  claim 16 , where the substituted alkyl group is a methyl group substituted with at least one halogen atom. 
     
     
       18. The process according to  claim 17 , where the at least one halogen atom is chlorine or bromine. 
     
     
       19. The process according to  claim 13 , where R L  is a phenyl group substituted with a trifluoromethyl group and R S  is a methyl group substituted with a bromine atom, a chlorine atom or a methoxy group.